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Keywords {🔍}

samples, tumour, plasma, somatic, cancer, dna, pubmed, article, sequencing, variants, mutations, reads, google, scholar, patients, analysis, cfdna, mutational, detected, variant, cellfree, shared, matched, signature, cas, central, signatures, unique, number, size, detection, data, performed, coverage, frequency, genome, low, copy, fragments, fig, content, ctdna, allele, wgs, germline, high, cnas, breast, sample, study,

Topics {✒️}

dna double-strand break-repair circulating cell-free dna cell-free circulating dna cell-free nucleic acids cell-free dna comprises cell-free dna utilizing cell-free tumour dna fra3b/fhit-deficient cancer genome plasma cell–free dna high-intensity sequencing reveals arxiv13033997 q-bio [internet] article download pdf cell-free dna uk/projects/fastqc/ bolger high-throughput sequencing data ultra-sensitive variant caller uncovering cell-population heterogeneity minh duc cao & lachlan high-throughput sequencing datasets comprehensive genome-wide analysis high-coverage wgs analysis high-coverage wgs datasets cell stem cell sequence alignment/map format genome-wide methylation sequencing circulating tumor dna performed high-coverage wgs related subjects high-coverage wgs approaches low-coverage wgs analysis late-stage human malignancies high-coverage targeted sequencing low-frequency somatic clones low-coverage wgs approach droplet digital pcr cfdna di-nucleosome peak full access low-coverage wgs approaches nucleic acids res fragment size distribution tumour-derived somatic cnas tumour-derived somatic mutations �min-var-freq’ option low-tumour content samples tumour-derived genomic alterations cancer related mutations 150 bp paired-end sequencing supplementary information-supplementary tables high confidence variants broad institute [internet]

Schema {🗺️}

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         headline:Whole genome deep sequencing analysis of cell-free DNA in samples with low tumour content
         description:Circulating cell-free DNA (cfDNA) in the plasma of cancer patients contains cell-free tumour DNA (ctDNA) derived from tumour cells and it has been widely recognized as a non-invasive source of tumour DNA for diagnosis and prognosis of cancer. Molecular profiling of ctDNA is often performed using targeted sequencing or low-coverage whole genome sequencing (WGS) to identify tumour specific somatic mutations or somatic copy number aberrations (sCNAs). However, these approaches cannot efficiently detect all tumour-derived genomic changes in ctDNA. We performed WGS analysis of cfDNA from 4 breast cancer patients and 2 patients with benign tumours. We sequenced matched germline DNA for all 6 patients and tumour samples from the breast cancer patients. All samples were sequenced on Illumina HiSeqXTen sequencing platform and achieved approximately 30x, 60x and 100x coverage on germline, tumour and plasma DNA samples, respectively. The mutational burden of the plasma samples (1.44 somatic mutations/Mb of genome) was higher than the matched tumour samples. However, 90% of high confidence somatic cfDNA variants were not detected in matched tumour samples and were found to comprise two background plasma mutational signatures. In contrast, cfDNA from the di-nucleosome fraction (300 bp–350 bp) had much higher proportion (30%) of variants shared with tumour. Despite high coverage sequencing we were unable to detect sCNAs in plasma samples. Deep sequencing analysis of plasma samples revealed higher fraction of unique somatic mutations in plasma samples, which were not detected in matched tumour samples. Sequencing of di-nucleosome bound cfDNA fragments may increase recovery of tumour mutations from plasma.
         datePublished:2022-01-20T00:00:00Z
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            Cell-free tumour DNA
            Somatic mutations
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            Cancer Research
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      headline:Whole genome deep sequencing analysis of cell-free DNA in samples with low tumour content
      description:Circulating cell-free DNA (cfDNA) in the plasma of cancer patients contains cell-free tumour DNA (ctDNA) derived from tumour cells and it has been widely recognized as a non-invasive source of tumour DNA for diagnosis and prognosis of cancer. Molecular profiling of ctDNA is often performed using targeted sequencing or low-coverage whole genome sequencing (WGS) to identify tumour specific somatic mutations or somatic copy number aberrations (sCNAs). However, these approaches cannot efficiently detect all tumour-derived genomic changes in ctDNA. We performed WGS analysis of cfDNA from 4 breast cancer patients and 2 patients with benign tumours. We sequenced matched germline DNA for all 6 patients and tumour samples from the breast cancer patients. All samples were sequenced on Illumina HiSeqXTen sequencing platform and achieved approximately 30x, 60x and 100x coverage on germline, tumour and plasma DNA samples, respectively. The mutational burden of the plasma samples (1.44 somatic mutations/Mb of genome) was higher than the matched tumour samples. However, 90% of high confidence somatic cfDNA variants were not detected in matched tumour samples and were found to comprise two background plasma mutational signatures. In contrast, cfDNA from the di-nucleosome fraction (300 bp–350 bp) had much higher proportion (30%) of variants shared with tumour. Despite high coverage sequencing we were unable to detect sCNAs in plasma samples. Deep sequencing analysis of plasma samples revealed higher fraction of unique somatic mutations in plasma samples, which were not detected in matched tumour samples. Sequencing of di-nucleosome bound cfDNA fragments may increase recovery of tumour mutations from plasma.
      datePublished:2022-01-20T00:00:00Z
      dateModified:2022-01-20T00:00:00Z
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         Cell-free DNA
         Cell-free tumour DNA
         Somatic mutations
         Mutational signatures
         Cancer Research
         Oncology
         Surgical Oncology
         Health Promotion and Disease Prevention
         Biomedicine
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         Medicine/Public Health
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            name:Devika Ganesamoorthy
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            address:
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            address:
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      name:Sunil R. Lakhani
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               type:PostalAddress
            type:Organization
      name:Peter T. Simpson
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            address:
               name:Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Herston, Brisbane, Australia
               type:PostalAddress
            type:Organization
      name:Lachlan J. M. Coin
      affiliation:
            name:University of Queensland
            address:
               name:Institute for Molecular Bioscience, University of Queensland, St Lucia, Brisbane, Australia
               type:PostalAddress
            type:Organization
            name:The University of Melbourne
            address:
               name:Department of Clinical Pathology, The University of Melbourne, Parkville, Melbourne, Australia
               type:PostalAddress
            type:Organization
            name:The University of Melbourne
            address:
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               type:PostalAddress
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            name:Imperial College London
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               name:Department of Infectious Disease, Imperial College London, London, UK
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      email:[email protected]
PostalAddress:
      name:Institute for Molecular Bioscience, University of Queensland, St Lucia, Brisbane, Australia
      name:Department of Clinical Pathology, The University of Melbourne, Parkville, Melbourne, Australia
      name:Institute for Molecular Bioscience, University of Queensland, St Lucia, Brisbane, Australia
      name:Institute for Molecular Bioscience, University of Queensland, St Lucia, Brisbane, Australia
      name:Institute for Molecular Bioscience, University of Queensland, St Lucia, Brisbane, Australia
      name:Institute for Molecular Bioscience, University of Queensland, St Lucia, Brisbane, Australia
      name:Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Herston, Brisbane, Australia
      name:Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Herston, Brisbane, Australia
      name:Pathology Queensland, The Royal Brisbane & Women’s Hospital, Herston, Brisbane, Australia
      name:QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia
      name:Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Herston, Brisbane, Australia
      name:Institute for Molecular Bioscience, University of Queensland, St Lucia, Brisbane, Australia
      name:Department of Clinical Pathology, The University of Melbourne, Parkville, Melbourne, Australia
      name:Department of Microbiology and Immunology, The University of Melbourne, Parkville, Melbourne, Australia
      name:Department of Infectious Disease, Imperial College London, London, UK

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